Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke. METHODS: We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR. RESULTS: A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site. CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

Management of MitraClip Single-Leaflet Detachment with an Additional Clip and an Amplatzer Vascular Plug.

Single-leaflet detachment of the MitraClip is a mechanism of early failure, but management is challenging and often requires surgical repair. This case report describes a novel transcatheter approach to repairing severe mitral regurgitation after MitraClip single-leaflet detachment by placement of an additional clip and an Amplatzer vascular plug. (Level of Difficulty: Advanced.).

Comparison of Outcomes of Pericardiocentesis Versus Surgical Pericardial Window in Patients Requiring Drainage of Pericardial Effusions.

Comparative outcomes of patients undergoing pericardiocentesis or pericardial window are limited. Development of pericardial effusion after cardiac surgery is common but no data exist to guide best management. Procedural billing codes and Cleveland Clinic surgical registries were used to identify 1,281 patients who underwent either pericardiocentesis or surgical pericardial window between January 2000 and December 2012. The 656 patients undergoing an intervention for a pericardial effusion secondary to cardiac surgery were also compared. Propensity scoring was used to identify well-matched patients in each group. In the overall cohort, in-hospital mortality was similar between the group undergoing pericardiocentesis and surgical drainage (5.3% vs 4.4%, p = 0.49). Similar outcomes were found in the propensity-matched group (4.9% vs 6.1%, p = 0.55). Re-accumulation was more common after pericardiocentesis (24% vs 10%, p <0.0001) and remained in the matched cohorts (23% vs 9%, p <0.0001). The secondary outcome of hemodynamic instability after the procedure was more common in the pericardial window group in both the unmatched (5.2% vs 2.9%, p = 0.036) and matched cohorts (6.1% vs 2.0%, p = 0.022). In the subgroup of patients with a pericardial effusion secondary to cardiac surgery, there was a lower mortality after pericardiocentesis in the unmatched group (1.5% vs 4.6%, p = 0.024); however, after adjustment, this difference in mortality was no longer present (2.6% vs 4.5%, p = 0.36). In conclusion, both pericardiocentesis and surgical pericardial window are safe and effective treatment strategies for the patient with a pericardial effusion. In our study there were no significant differences in mortality in patients undergoing either procedure. Observed differences in outcomes with regard to recurrence rates, hemodynamic instability, and in those with postcardiac surgery effusions may help to guide the clinician in management of the patient requiring therapeutic or diagnostic drainage of a pericardial effusion.

Associations Between Cardiac Troponin, Mechanism of Myocardial Injury, and Long-Term Mortality After Noncardiac Vascular Surgery.

BACKGROUND: The time-sensitive hazard of perioperative cardiac troponin T (cTnT) elevation and whether long-term mortality differs by mechanism of myocardial injury are poorly understood. METHODS AND RESULTS: In this observational study of 12 882 patients who underwent noncardiac vascular surgery, patients were assessed for cTnT sampling within 96 hours postoperatively. Mortality out to 5-years was stratified by cTnT level and mechanism of myocardial injury. During a median follow-up of 26.9 months, there were 2149 (16.7%) deaths. By multivariable Cox proportional hazards analysis, there was a graded increase in mortality with any detectable cTnT compared to <0.01 ng/mL; cTnT 0.01 to 0.029 ng/mL hazard ratio (HR) 1.54 (95% CI 1.18-2.00, P=0.002), 0.03 to 0.099 ng/mL HR 1.86 (95% CI 1.49-2.31, P<0.001), 0.10 to 0.399 ng/mL HR 1.83 (95% CI 1.46-2.31, P<0.001), ≥0.40 ng/mL HR 2.62 (95% CI 2.06-3.32, P<0.001). Mortality for each mechanism of injury was greater than for patients with normal cTnT; baseline cTnT elevation HR 1.71 (95% CI 1.31-2.24; P<0.001), Type 2 myocardial infarction HR 1.88 (95% CI 1.57-2.24; P<0.001), Type 1 MI HR 2.56 (95% CI 2.56, 1.82-3.60; P<0.001). On Kaplan-Meier analysis, long-term survival did not differ between mechanisms. The hazard of mortality was greatest within the first 10 months postsurgery. Consistent results were obtained in confirmatory propensity-score matched analyses. CONCLUSIONS: Any detectable cTnT ≥0.01 ng/mL is associated with increased long-term mortality after vascular surgery. This risk is greatest within the first 10 months postoperatively. While short-term mortality is greatest with Type 1 myocardial infarction, long-term mortality appears independent of the mechanism of injury.

Managing hypertension in type 2 diabetes mellitus.

Hypertension is a common problem in the diabetic population with estimates suggesting a prevalence exceeding 60%. Comorbid hypertension and diabetes mellitus are associated with high rates of macrovascular and microvascular complications. These two pathologies share overlapping risk factors, importantly central obesity. Treatment of hypertension is unequivocally beneficial and improves all-cause mortality, cardiovascular mortality, major cardiovascular events, and microvascular outcomes including nephropathy and retinopathy. Although controversial, current guidelines recommend a target blood pressure in the diabetic population of <140/90 mmHg, which is a similar target to that proposed for individuals without diabetes. Management of blood pressure in patients with diabetes includes both lifestyle modifications and pharmacological therapies. This article reviews the evidence for management of hypertension in patients with type 2 diabetes mellitus, and provides a recommended treatment strategy based on the available data.

Troponin elevation after noncardiac surgery: Significance and management.

How to interpret and manage troponin elevations after noncardiac surgery is a common clinical question for cardiologists and internists. An estimated 5% to 25% of patients who undergo noncardiac surgery have an elevated postoperative troponin level. Patients with troponin elevation are at higher short-term and long-term risk of morbidity and mortality. Current guidelines provide few recommendations on how to manage these patients. The authors review the evidence and guidelines and propose treatment strategies.

Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals.

OBJECTIVES: This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals. BACKGROUND: Current data regarding the outcome of patients with concealed LQTS are limited. METHODS: Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤ 440 ms [n = 469]), LQTS with prolonged QTc interval (> 440 ms [n = 1,392]), and unaffected family members (genotyped negative with ≤ 440 ms [n = 1,525]). RESULTS: The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age > 13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). CONCLUSIONS: Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.

Ion channel mechanisms related to sudden cardiac death in phenotype-negative long-QT syndrome genotype-phenotype correlations of the KCNQ1(S349W) mutation.

UNLABELLED: BACKGROUND: Data regarding possible ion channel mechanisms that predispose to ventricular tachyarrhythmias in patients with phenotype-negative long-QT syndrome (LQTS) are limited. METHODS AND RESULTS: We carried out cellular expression studies for the S349W mutation in the KCNQ1 channel, which was identified in 15 patients from the International LQTS Registry who experienced a high rate of cardiac events despite lack of significant QTc prolongation. The clinical outcome of S349W mutation carriers was compared with that of QTc-matched carriers of haploinsufficient missense (n = 30) and nonsense (n = 45) KCNQ1 mutations. The channels containing the mutant S349W subunit showed a mild reduction in current (<50%), in the haploinsuficient range, with an increase in maximal conductance compared with wild-type channels. In contrast, expression of the S349W mutant subunit produced a pronounced effect on both the voltage dependence of activation and the time constant of activation, while haploinsuficient channels showed no effect on either parameter. The cumulative probability of cardiac events from birth through age 20 years was significantly higher among S349W mutation carriers (58%) as compared with carriers of QTc-matched haploinsufficent missense (21%, P = 0.004) and nonsense (25%, P = 0.01) mutations. CONCLUSIONS: The S349W mutation in the KCNQ1 potassium channel exerts a relatively mild effect on the ion channel current, whereas an increase in conductance compensates for impaired voltage activation of the channel. The changes observed in voltage activation of the channel may underlie the mechanisms predisposing to arrhythmic risk among LQTS patients with a normal-range QTc.

Total serum bilirubin does not affect vascular reactivity in patients with diabetes.

Bilirubin may have a major role in the prevention of cardiovascular disease based on recent data regarding its anti-oxidant properties. We determined the relationship between total serum bilirubin and vascular reactivity in a large cohort of individuals with diabetes, a disease associated with known oxidant stress. We studied 302 individuals: 52 controls, 37 with type 1 diabetes, 213 with type 2 diabetes. High-resolution ultrasound was used to measure flow-mediated dilation (FMD; endothelium-dependent) and nitroglycerin-induced dilation (NID, endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure microvascular reactivity in the forearm skin before and after iontophoresis of acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent). Bilirubin levels were higher in the type 2 diabetes group (0.71 +/- 0.34 mg/dl) compared to controls (0.56 +/- 0.26 mg/dl, p < 0.0001). A weak inverse correlation was observed between bilirubin and FMD (r = -0.125, p = 0.032) and skin endothelium-dependent vasodilation (r = -0.157, p = 0.019). In multivariate analyses, however, these correlations were not statistically significant. There is no association between bilirubin levels and vascular reactivity in the macro- and microcirculation of individuals with diabetes. Bilirubin, therefore, does not correlate with predictors of cardiovascular risk in the diabetic population.

Prolonged mechanical noise restores tactile sense in diabetic neuropathic patients.

Acute application of stochastic resonance (SR), defined as a subsensory level of mechanical noise presented directly to sensory neurons, improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy. This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function. Twenty diabetic patients were studied. The effect of stimulation was measured at 2 time points, at the beginning and after 60 minutes of continual SR stimulation. This effect was measured using the vibration perception threshold (VPT) at the big toe under 2 conditions: a null (no SR) condition and active SR, defined as mechanical noise below the subject's own threshold of perception. The measurements under null and active conditions were done randomly and the examiner was blinded regarding the type of condition. Immediately after SR application, the VPT with SR in null condition was similar to baseline (32.2 +/- 13.1, P = nonsignificant) but was significantly lower during active SR (27.4 +/- 11.9) compared with both baseline (P = .018) and off position (P = .045). The 60 minutes VPT with active SR (28.7 +/- 11.1) reached significance comparing the baseline when one outlier was removed from the analysis (P = .031). It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy. These results permit the conclusion that there is no short-term adaptation to the stimulation signal. Long-term application of this technique, perhaps in the form of a continually vibrating shoe insert, or insole, may result in sustained improvement of nerve function.